Table 2 Confirmed IEM by WES. n = 14

tRNA Ala

m.5591G > A^b (16476954)

MTTA (590000)

Failure to thrive, ptosis, myopathy, normal mitochondrial studies on muscle biopsy.

ND5

m.13513G > A (p.D393N)^b (12509858)

MTND5 (516005)

Developmental regression, dysmorphic features, esotropia, chorioretinal atrophy, seizure, left ventricular hypertrophy, renal insufficiency, brain image suggestive of Leigh syndrome.

PDHA1 (NM_000284)

c.787C > G (p.R263G) (1508605)

PDHAD (312170)

Brain image suggestive of Leigh syndrome; low complex II (succinate dehydrogenase) activity in the fibroblasts. Two heterozygous (‘cis’ configuration) novel missense variants, c.321C > G (p.1107 M) and c.338A > T (p.N113I), in SDHA were found in patient and father.

FBXL4 (NM_012160)

c.1067delG (p.G356fs) (23993194)

MTDPS13 (615471)

Developmental regression, hypotonia, failure to thrive, microcephaly, lactic acidosis, normal fibroblast mitochondrial studies. Three siblings died in infancy.

C10orf2 (NM_021830)

c.1198C > T (p.R400C) (21364701)

MTDPS7 (271245)

Developmental regression, hearing loss, scoliosis, reduced activities of complexes I & IV in myocytes; normal activities in fibroblasts. Two cousins with Leigh disease.

MTHFR (NM_005957)

c.1596C > G(p.Y532) ^(a)

MTHFRD (236250)

Progressive encephalopathy, seizure, cerebral venous thrombosis, gangrenous like bullous formation in the leg, congenital heart disease, ↑homocysteine, ↓methionine.

PYCR2 (NM_013328)

c.28C > T(p.Q10X) ^(a)

HLD10 (616420)

Developmental regression, failure to thrive, seizure, microcephaly, severe demyelination, thin corpus callosum.

c.796C > T(p.R266X) ^(a)

Developmental delay, hypotonia, failure to thrive, microcephaly, thin corpus callosum, delayed myelination.

HEXA (NM_000520)

c.2 T > C

Tay-Sachs (268800)

Developmental regression, failure to thrive, seizure disorders, dystonia, feeding difficulties constipation. Diagnosis confirmed by enzyme analysis.

HEXB (NM_000521)

c.826_829del (p.E276fs)

Sandhoff (268800)

Developmental regression, failure to thrive, feeding difficulties, seizure, and vision loss.

SUMF1 (NM_182760)

c.691dupT (p.W231fs) c.689A > G (p.E230ZG)

MSD (272200)

Developmental delay, seizure, hepatomegaly, delayed myelination, ↑urine sulfatide, ↑urine heparan sulphate.

UROC1 (NM_144639)

c.855G > A (p.W285X) ^(a)

UROCD (276880)

Intellectual disabilities, attention deficit and hyperactivity disorder, hyperextensible joints, ↑imidazole propionate.

TBX19 (NM_005149)

c.604-1G > C ^(a)

IAD (201400)

Intellectual disabilities, congenital hypothyroidism, two sisters died in infancy with hypoglycemia.

HSD3B7 (NM_025193)

c.45_46del (p.G17fs) (12679481)

CBAS1 (607765)

Neonatal cholestasis, hepatosplenomegaly, hypotonia, failure to thrive.